Modification of serum lipids and cardiovascular risk by estrogenic active compounds

Abstract

Cardiovascular disease is an important cause of death among women. After the menopause there is a steep elevation of low-density lipoprotein (LDL) cholesterol and lipoprotein(a) concomitantly with other risk factors ,followed by a striking increase in arteriosclerotic vascular disease ,compatible with a lack of estrogens as a causative factor. The benefit of hormone replacement therapy has been documented in several large studies ,although rigorous randomized trials are still under way. However ,cardiovascular events have been reduced by approximately 50%. In order to optimize beneficial effects and minimize side-effects ,the characteristics of selective estrogenic active compounds are a major target of research. The anti-estrogens are the prototype of partial and selective estrogen functions. The components of conjugated estrogens are under investigation for their specific effects. For example ,both 17 f -dihydroequilin sulfate and 17 f -dihydroequilenin sulfate seem to exert antioxidant activity without significant proliferative effects on uterine or breast tissues. This suggests a selective estrogenic activity dependent on the predominant type of estrogen receptor in the particular tissue. Equilin sulfate exerts a significantly stronger antioxidant activity than 17 g -estradiol in vitro ,and j 8-estrone sulfate increases the lag time for low-density lipoprotein oxidation in vivo . These actions on lipoproteins may add to the quantitative changes of lipoproteins ,while other effects are independent of lipoproteins. The 17 f -dihydroequilin sulfate and equilin sulfate improved the action of insulin in vivo . Data from rhesus monkeys treated with 17 f -dihydroequilenin sulfate indicate that additional mechanisms are probably responsible for the observed cardiovascular protection. Further studies need to be conducted in order to identify selective estrogen receptor modulators and assess their potential ,especially in lowering cardiovascular risk.